Affinity of Rimantadine Enantiomers against Influenza A/M2 Protein Revisited

Antonios Drakopoulos, Christina Tzitzoglaki, Chulong Ma, Kathrin Freudenberger, Anja Hoffmann, Yanmei Hu, Günter Gauglitz, Michaela Schmidtke, Jun Wang, Antonios Kolocouris

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Recent findings from solid state NMR (ssNMR) studies suggested that the (R)-enantiomer of rimantadine binds to the full M2 protein with higher affinity than the (S)-enantiomer. Intrigued by these findings, we applied functional assays, such as antiviral assay and electrophysiology (EP), to evaluate the binding affinity of rimantadine enantiomers to the M2 protein channel. Unexpectedly, no significant difference was found between the two enantiomers. Our experimental data based on the full M2 protein function were further supported by alchemical free energy calculations and isothermal titration calorimetry (ITC) allowing an evaluation of the binding affinity of rimantadine enantiomers to the M2TM pore. Both enantiomers have similar channel blockage, affinity, and antiviral potency.

Original languageEnglish (US)
Pages (from-to)145-150
Number of pages6
JournalACS Medicinal Chemistry Letters
Volume8
Issue number2
DOIs
StatePublished - Feb 9 2017

Keywords

  • antiviral assay
  • Bennett’s acceptance ratio
  • electrophysiology
  • free energy perturbation
  • influenza M2 pore
  • isothermal titration calorimetry
  • membrane protein
  • Rimantadine enantiomers
  • synthesis

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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  • Cite this

    Drakopoulos, A., Tzitzoglaki, C., Ma, C., Freudenberger, K., Hoffmann, A., Hu, Y., Gauglitz, G., Schmidtke, M., Wang, J., & Kolocouris, A. (2017). Affinity of Rimantadine Enantiomers against Influenza A/M2 Protein Revisited. ACS Medicinal Chemistry Letters, 8(2), 145-150. https://doi.org/10.1021/acsmedchemlett.6b00311